Is OCRL p.Ser256= (c.768C>T) pathogenic?

OCRL p.Ser256= (c.768C>T) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-15). Very rare (popmax 0.00297%, eas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Ser256= (c.768C>T)?

OCRL p.Ser256= (c.768C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ser256= (c.768C>T) in the general population?

OCRL p.Ser256= (c.768C>T) is very rare (popmax 0.00297%, eas) (gnomAD).

OCRL p.Ser256=

c.768C>T · rs1368090073 · VCV1513241

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00297%, eas)

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Pangolin	Δ0.22	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -1	GERP -5.9, phastCons 0.004
Overall
CADD	4.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% East Asian · 1/33,722 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000415% 5/1,203,798 alleles · very rare exomes 5/1,090,064 · genomes 0/113,734 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00297%	33,722
Admixed American	0.00218%	45,966
South Asian	0.00176%	56,814
European (non-Finnish)	0.000225%	444,399

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OCRL
Protein: p.Ser256=
Coding: c.768C>T
MANE Select: NM_000276
dbSNP: rs1368090073
Type: single nucleotide variant
Location: chrX:129560595 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 256: the 5-ppase domain

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oculocerebrorenal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL c.1714-1G>A Pathogenic ★★ same condition
OCRL c.2256+1G>T Likely pathogenic ★★ same condition
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same condition
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
OCRL p.Arg318Cys Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Arg318His Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ocrl-p-ser256 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown